Cancer is a genetic disease caused by genetic instability. Our program in cancer genetics includes a component that emphasizes high throughput refined karyotypic analysis and comprehensive cloning and characterization of all chromosomal aberrations found to be present in specific cancers or cancer cell lines. We have dubbed an aspect of this approach, spectral cloning. Another major component involves the development of a patient pathway that emphasizes individualized risk screening, education, counseling, germline testing (for those who choose to be tested), followed by entry into protocols for prevention, surveillance, and targeted therapy. The two prototype cancers for which this program has been initiated are colorectal and breast cancer. In addition we have begun a program of complex trait genetic analysis based on the genetics of smoking cessation. The translational research component that supports this program includes mulecular diagnostics, biomarkers of risk, genotype/phenotype correlations, and new drug screening assay invention. In addition, we are invested in new initiatives that are attempting to link the human physical genomic map with the cytogenetic map, and to provide a database and clone repository that can be utilized by the biomedical community at large.